1. Field of the Invention
The present invention relates to benzenesulfonamide derivatives and a pharmaceutical composition thereof and, more particularly, to benzenesulfonamide derivatives used as a cell-cycle inhibitor for treating solid tumors and a pharmaceutical composition thereof.
2. Description of Related Art
In the recent years, it is found that foods or food additives, and environmental pollutions are blamed for directly causing cancer. In addition, tobacco smoke is also a powerful carcinogen causing the deaths of millions. Hence, not only in Taiwan, but also in the developed countries around the whole world, the incidence rates of cancers are quite high. According to the data published by the American Cancer Society, cancer is perhaps the most significant threat to public health. In addition, according to the data published by Department of Health in Taiwan, cancer is the first among the 10 leading causes of death since 1982. Solid tumors of lung cancer, liver cancer, and colorectal cancer are the most common tumors causing death, and the death rate of these cancers is about 50% of all cancer deaths. Recently, anti-cancer drugs of etoposide and cisplatin have been developed, which are effective in the treatment of leukemia and lymph cancer. However, the curative effect of these drugs on lung cancer, liver cancer, and colorectal cancer is not good enough.
Currently, a surgical operation can be performed to cut the cancer cell and partial lymph gland to treat the solid tumors such as gastric cancer. Also, some other treatments such as radiotherapy, chemotherapy, and immune therapy have been developed to treat cancers. In the recent years, the development of several therapeutic agents has lead to treatment cancers through new anti-cancer mechanisms, and it has been proved that the survival rate of patients can be increased by treating them with these therapeutic agents. These therapeutic agents can treat tumor cells through inhibiting cell cycle progression, angiogenesis, farnesyl transferase, and tyrosine kinases. Recently, the therapeutic agent for inhibiting the cell cycle progression, such as wortmannin, 5-fluorouracil, daunomycin, and colchicines are the most potential anti-cancer drugs.
Eisai Co., Ltd. has investigated two kinds of benzenesulfonamide derivatives, which have already entered clinical trials. The formulas of these two benzenefulfonamide derivatives are represented as follow:

These two benzenesulfonamide derivatives are inhibitors of the cell cycle, and cause cell death. E7010 shows great effect on the test for anti-cancer activity in mice, and has already entered phase II clinic trials. In addition, E7070 has the best anti-cancer activity among the benzenesulfonamide derivatives, and has already entered phase II clinic trials. It has been proved that E7070 can inhibit human colon cancer cell (colon 38), and the IC50 of E7070 is 0.26 μM (Owa et. al., J. Med. Chem. 1999, 42, 3789-3799). However, although these benzenesulfonamide derivatives have already entered clinical trials, whether these therapeutic agents can be used in the cancer treatment is still unknown.
Several therapeutic agents have been applied on the treatment of solid tumors. However, not all of them are effective due to different locations of tumor cells, different patients, and side effects generated therefrom. Because cancer is the first among the 10 leading causes of death, and solid tumors are the most common tumors causing death, it is urgent to investigate therapeutic agents for inhibiting solid tumor cells. Hence, there is a long unfulfilled need for the present invention which provides a new compound for treating solid tumors, and inhibiting the growth of the tumor cells.